Neuronal excitability requires the summation of post-synaptic potentials to attain threshold for the propagation of a burst of action potentials. In CA1 hippocampal pyramidal neurons, small conductance Ca2+-activated K+ (SK) channels are believed to underlie the two Ca2+-dependent components of the afterhyperpolarization (AHP). These SK channels can be activated synaptically suggesting that they may contribue to excitatory post-synaptic potentials (EPSPs). By modulating both the magnitude and duration of EPSPs, SK channel activity may determine whether a post-synaptic CA1 neuron reaches threshold for action potential propagation. By modulating action potential bursting patterns and EPSPs, these channels potentially contribute to the most fundamental role of CA1 neurons in physiology: the integration of learning and memory. Consistent with this proposal is the observation that pharmacological modulation of SK channels in vivo stimulates hippocampal-dependent learning in mice. Three distinct SK channel subunits, SK1, SK2 and SK3, have been cloned and all are expressed in CA1 neurons. Because of the potential neurophysiologcal importance of these channels, the overall aim of this proposal is to investigate the physiological contribution of these different SK channel subunits to the AHP, spike frequency adaptation, and EPSPs of CA1 neurons. To test, I will investigate SK transgenic mice in which SK expression is regulated acutely and post-developmentally in a tissue specific manner.